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Your search keyword '"Reichenbach, P."' showing total 27 results
Start Over Author "Reichenbach, P." Publisher american chemical society
27 results on '"Reichenbach, P."'

26. Azole-Based Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Author

Röhrig UF, Majjigapu SR, Reynaud A, Pojer F, Dilek N, Reichenbach P, Ascencao K, Irving M, Coukos G, Vogel P, Michielin O, and Zoete V

Subjects
Azoles chemical synthesis, Azoles metabolism, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors metabolism, HEK293 Cells, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Molecular Dynamics Simulation, Molecular Structure, Protein Binding, Quantitative Structure-Activity Relationship, Azoles pharmacology, Enzyme Inhibitors pharmacology, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors
Abstract

The heme enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays an essential role in immunity, neuronal function, and aging through catalysis of the rate-limiting step in the kynurenine pathway of tryptophan metabolism. Many IDO1 inhibitors with different chemotypes have been developed, mainly targeted for use in anti-cancer immunotherapy. Lead optimization of direct heme iron-binding inhibitors has proven difficult due to the remarkable selectivity and sensitivity of the heme-ligand interactions. Here, we present experimental data for a set of closely related small azole compounds with more than 4 orders of magnitude differences in their inhibitory activities, ranging from millimolar to nanomolar levels. We investigate and rationalize their activities based on structural data, molecular dynamics simulations, and density functional theory calculations. Our results not only expand the presently known four confirmed chemotypes of sub-micromolar heme binding IDO1 inhibitors by two additional scaffolds but also provide a model to predict the activities of novel scaffolds.

Published
2021
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27. Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase.

Author

Iyisan B, Janke A, Reichenbach P, Eng LM, Appelhans D, and Voit B

Subjects
Fluorescent Dyes chemistry, Hydrogen-Ion Concentration, Infrared Rays, Microscopy, Atomic Force, Surface Properties, Photochemistry, Polyethylene Glycols chemistry
Abstract

Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane-β-cyclodextrin host-guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young's modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors.

Published
2016
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